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\begin{document}

\title{Metastatic Signet Ring Gastric Carcinoma Bypassing Virchow's node: An
Unexpected Etiology of a Painful Neck Mass.}



\author[1]{Arianna Di Stadio}%
\author[2]{Luca D'Ascanio}%
\author[2]{Gino Latini}%
\author[2]{Paolo Gradoni}%
\author[2]{Manlio Pandolfini}%
\author[2]{Tiziana Tamburrano}%
\author[3]{Giampietro Ricci}%
\author[4]{Massimo Maranzano}%
\author[5]{Michael Brenner}%
\affil[1]{University of Perugia School of Medicine and Surgery}%
\affil[2]{Ospedali Riuniti Marche Nord Presidio ospedaliero Santa Croce}%
\affil[3]{University of Perugia Department of Medicine}%
\affil[4]{Manchester University NHS Foundation Trust}%
\affil[5]{University of Michigan}%


\vspace{-1em}



  
  \date{May 07, 2024}


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\selectlanguage{english}
\begin{abstract}
Neck masses can be a challenge because several cancers metastasize in
this area. Head and neck tumors are more commonly responsible of lymph
nodes in neck. However, also gastric cancer can be metastatic in this
area. We present a rare case of neck gastric meta with negative
Virchow's lymph node.%
\end{abstract}%



\sloppy


\textbf{Metastatic Signet Ring Gastric Carcinoma Bypassing Virchow's
node: An Unexpected Etiology of a Painful Neck Mass.}

\textbf{Arianna Di Stadio, MD, PhD\textsuperscript{3*}, Luca D'Ascanio
MD\textsuperscript{1*}, Gino Latini MD\textsuperscript{1}, Paolo Gradoni
MD\textsuperscript{1}, Manlio Pandolfini MD\textsuperscript{1}} ,

\textbf{Tiziana Tamburrano MD\textsuperscript{2}, Giampietro Ricci
MD\textsuperscript{3}, Massimo Maranzano\textsuperscript{4} and Michael
J Brenner MD\textsuperscript{5}}

\textsuperscript{1}: Department of Head and Neck Surgery, Institute of
Otorhinolaryngology, Santa Croce Hospital AORMN, Fano, Italy

\textsuperscript{2}: Institute of Oncology, Santa Croce Hospital AORMN,
Fano, Italy

\textsuperscript{3}: Department of Otolaryngology, University of
Perugia, Perugia, Italy

\textsuperscript{4}: CFU of Head and Neck Surgery, Division of Oral and
Maxillofacial and Facial Plastic Surgery

Manchester University Foundation Trust

\textsuperscript{5}: Department of Otolaryngology-Head and Neck Surgery,
University of Michigan, Ann Arbor, MI, USA

*: equal contribution

Corresponding author: Dr. Arianna Di Stadio, Otolaryngology Department,
Piazza Menghini 1, 06129 Perugia, Italy. E-mail:
ariannadistadio@hotmail.com; arianna.distadio@unipg.it

Running title: Neck Metastasis with Unknown Primary

\textbf{ABSTRACT:} Neck masses can be a challenge because several
cancers metastasize in this area. Head and neck tumors are more commonly
responsible of lymph nodes in neck. However, also gastric cancer can be
metastatic in this area. We present a rare case of neck gastric meta
with negative Virchow's lymph node.

\textbf{KEYWORDS:} Neck mass, neck pain, lymph node, Virchow's lymph
node, gastric cancer, head cancer, differential diagnosis.

\textbf{KEY CLINICAL MESSAGE:} Neck lymph nodes are common metastases of
head and neck tumors. Other tumors, i.e gastric one, metastasize firstly
in the clavicular fossa and then in the neck. Our case describes a rare
gastric tumor with neck meta and negative Virchow' s lymph node.

\textbf{INTRODUCTION}

Despite clinical practice guidelines to guide evaluation and management
of neck masses {[}1{]}, the diverse etiologies of neck masses may make
accurate diagnosis challenging {[}2{]}. A neck mass in an adult most
often represents lymphatic transit of metastasis from a mucosal squamous
cell carcinoma or less commonly a primary tumor. Visceral malignancy
{[}3{]} may also affect the head and neck, usually via lymphatic spread
that classically presents as an enlarged Virchow's lymph node (VN), a
left-sided supraclavicular fossa lymph node. Muscle metastasis may also
occur via hematogenous spread {[}4,5{]}. We describe a rare case of
signet ring cell-variant gastric adenocarcinoma that bypassed Virchow's
node to involve the posterolateral neck.

\textbf{CASE PRESENTATION}

A 78-year-old white woman presented with a 6-month history of
progressive left neck swelling, and she had recently developed pain on
lateral neck movement. She had no other symptoms, and her medical
history was negative history except for a clear cell renal cell
carcinoma~removed in May 2014 and without recurrence. Exam demonstrated
a firm, hypomobile mass of the Level V neck, without any palpable masses
in the clavicular fossa or other regions of the neck. Flexible endoscopy
revealed no evident mucosal lesions of the upper aerodigestive tract,
and ultrasound-guided biopsy was non-diagnostic.

Because of her cancer history, neck magnetic resonance imaging (MRI)
with gadolinium, neck and thorax contrast computed tomography (CT), and
total body Positron Emission Tomography (PET) CT were performed. Head
and neck MRI (\textbf{Figure 1AB} ) and CT (\textbf{Figure 1CD} )
imaging demonstrated an enhancing posterolateral neck lesion measuring
37 x 35 x 15 mm mass adjacent to and invading the sternocleidomastoid
muscle. Thoracic imaging did not show presence of masses or lymph
nodes.\textbackslash{}sout. Repeat fine needle aspirates performed under
ultrasound guidance were non-diagnostic; the patient wished surgical
removal and was therefore taken to surgery for endoscopy of the upper
respiratory tract, excisional biopsy of the mass, and plan for formal
neck dissection if squamous cell carcinoma was identified. Endoscopy
showed no abnormality, and removal of the neck mass was performed with
surrounding fibro-adipose tissue and sternocleidomastoid muscle.

Pathology of frozen section demonstrated cellular atypia consistent with
gastric carcinoma (\textbf{Figure 2 ABC)} . Subsequent gastric endoscopy
(performed under general anesthesia) identified a gastric ulcer located
in the larger curvature of the stomach/anterior wall of pre-pyloric
area. Several biopsies were performed in the stomach close and far from
the identified lesion. The histologic analysis of the finding confirmed
the diagnosis of signet-ring cell carcinoma pathology, HER2 negative.

Following multidisciplinary review, the patient started chemotherapy
with FOLFOX. There was tumor progression despite therapy, and the
regimen was therefore changed to FOLFIRI, with tumor regression at
10-months. The patient was still in remission at the last follow-up in
August 2020.

\textbf{DISCUSSION}

This case underscores importance of definitive diagnosis for head and
neck masses and is a reminder of the diverse etiologies for tumors in
this region {[}4{]}. There was no suggestion of visceral disease on
clinical presentation {[}4{]}. The patient denied gastric pain,
decreased appetite, or weight loss {[}6{]}, consistent with the finding
of metastases in 80\% of patients with gastric cancer at time of
diagnosis {[}7{]}; for this reason, Suh et al. suggested to perform
excisional biopsy of suspect lymph node to detect these tumors in early
stage {[}8{]}. Metastasis of gastric cancer to the head and neck is less
common {[}5{]}, although VN (Troisier's sign) is well recognized
{[}3{]}.

The Virchow's node observed in visceral malignancy arises from tumor
metastasis via the thoracic duct, so it very very rare observing a jump
in the lymph nodes station during cancer metastasizing {[}9,10{]}. VN
may compress or invade neurovascular structures, causing thoracic outlet
syndrome, brachial plexopathy, phrenic neuropathy, or Horner's syndrome.
Because of diverse sources of visceral malignancy, including
gastrointestinal, hepatobiliary, and other origins, Virchow's node and
its variants are important across surgical specialties. Diagnosis of
neck masses is inherently challenging, and the presence of V level lymph
node without Virchow's node is an atypical presentation that may obscure
the source of the primary tumor. The most important point of this
clinical case is the extreme rarity in identifying V lymph node without
Virchow's node involvement {[}10{]}, in fact, another case only has been
reported in literature in 2008 by Takashima et al {[}11{]}.

\textbf{FUNDING} : none.

\textbf{FINANCIAL DISCLOSURE/CONFLICT OF INTEREST:} The authors have no
financial conflicts of interest relevant to this article to disclose.

\textbf{ETHICAL APPROVAL AND CONSENT TO PARTECIPATE:} the study was
approved by the IRB of the hospital without releasing of an
authorization number. The patient signed a written consent before being
included in the study.

\textbf{PATIENT CONSENT FOR PUBLICATION:} the patient authorized to
publish her data previous anonymization.

\textbf{AVAILABILITY OF DATA AND MATERIALS:} original data are available
under request to the corresponding author.

\textbf{AUTHORS' CONTRIBUTION:} ADS, LdA, MB: study design and article
writing; GL, PG, MP and TT collection of clinical data; GR and MM
literature review, criticism and review of paper.

\textbf{ACKNOWLEDGEMENT:} not applicable

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Pynnonen MA, Gillespie MB, Roman B, et al. Clinical Practice
  Guideline: Evaluation of the Neck Mass in Adults.~Otolaryngol Head
  Neck Surg. 2017;157: S1-S30.
\item
  Haynes J, Arnold KR, Aguirre-Oskins C et al. Evaluation of neck masses
  in adults. Am Fam Physician. 2015; 91:698-706.
\item
  Aghedo BO, Kasi A. Virchow Node. SourceStatPearls {[}Internet{]}.
  Treasure Island (FL): StatPearls Publishing; 2020.
\item
  Aguirre LE, Salcedo J, Zuquello R et al. Metastatic involvement of
  skeletal muscle from gastric adenocarcinoma. Oxf Med Case Reports.
  2019; 2019: omz081.
\item
  Goto S, Takeda H, Sasahara Y et al. Metastasis of advanced gastric
  cancer to the extraocular muscle: a case report. J Med Case Rep. 2019;
  13:107.
\item
  Sundriyal D, Kumar N, Dubey SK et al. Virchow's node. BMJ Case Rep.
  2013; pii: bcr2013200749.
\item
  Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F.
  Gastric cancer: descriptive epidemiology, risk factors, screening, and
  prevention.~\emph{Cancer Epidemiol Biomarkers Prev} .
  2014;23(5):700-713. doi: 10.1158/1055-9965.EPI-13-1057
\item
  Suh YS, Yang HK. Screening and Early Detection of Gastric Cancer: East
  Versus West.~\emph{Surg Clin North Am} . 2015;95(5):1053-1066. doi:
  10.1016/j.suc.2015.05.012
\item
  Zdilla MJ, Aldawood AM, Plata A, Vos JA, Lambert HW. Troisier sign and
  Virchow node: the anatomy and pathology of pulmonary adenocarcinoma
  metastasis to a supraclavicular lymph node.~\emph{Autops Case Rep} .
  2019;9(1): e2018053. Published 2019 Feb 25. doi:10.4322/acr.2018.053.
\item
  L\selectlanguage{ngerman}ópez F, Rodrigo JP, Silver CE, et al. Cervical lymph node metastases
  from remote primary tumor sites.~\emph{Head Neck} . 2016;38 Suppl
  1(Suppl 1):E2374-E2385. doi:10.1002/hed.24344
\item
  Takashima T, Nakata B, Hatama M, et al. Gastric cancer with cervical
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\end{enumerate}

\textbf{FIGURE LEGENDS}

\emph{Figure 1:} \textbf{AB)} MRI showing a metastatic lesion of the
neck with histology from primary lesion. Coronal contrast-enhanced
T1-weighted MRI slices show the enhancing lesion of the left
posterolateral neck (asterisks). The lesion's location, encroaching on
sternocleidomastoid musculature and prevertebral fascia, correlates with
clinical symptoms of neck pain with lateral movement. \textbf{CD)} CT
scan parasagittal and coronal view confirmed the presence of the mass
(asterisk) and how it infiltrates surrounding structures. The round
circle indicates norma lymph node.

\emph{Figure 2}\textbf{: Histology 200x magnification. A)} Incisional
biopsies of the left sternocleidomastoid muscle and superficial cervical
fascia. Hematoxylin-eosin staining shows histological features
suggestive of infiltrating gastric carcinoma (G2). \textbf{B)} Immune
histochemistry with CKAE1/AE3 shows positive nuclear coloration
indicative of cancer. \textbf{C)} Eosin and hematoxylin staining of
gastric tissue from endoscopy shows classic histology of signet-ring
cell carcinoma with characteristic signet-ring cell vacuoles (black
arrow).\selectlanguage{english}
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